BOSS PD: Behavioral or Solifenacin Therapy for Urinary Symptoms in Parkinson Disease

Sponsor

VA Office of Research and Development (U.S. Fed)

Overall Status

Recruiting

CT.gov ID

NCT03149809

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

22.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The impact of urinary symptoms in Parkinson disease (PD) extends beyond worsened well-being. Urinary symptoms common in PD, especially incontinence and nocturia, are major risk factors for falls likely due to the combination of urinary urgency and impaired mobility (and falls are a leading cause of mortality in PD), for spouse/caregiver stress due to decreased mutuality in the relationship, and for institutionalization, largely due to increased disability. Additionally, most medications currently recommended for urinary symptoms in PD are anticholinergic and have the potential to worsen the progressive cognitive and autonomic burdens of the disease. Veterans with PD are also more likely to rely solely on VA for their health care than Veterans without PD. Thus, optimizing the care of urinary symptoms for Veterans with PD becomes imperative, particularly for VA. Using a non-inferiority design, this proposal seeks to demonstrate the comparative effectiveness of pelvic floor muscle exercise-based behavioral therapy versus drug therapy to treat urinary symptoms in PD.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder Parkinson Disease	Drug: solifenacin Behavioral: Pelvic floor muscle exercise-based behavioral therapy	Phase 3

Detailed Description

The number of persons with Parkinson Disease (PD) in the United States is expected to double by 2030 as the population ages. Importantly, this increase in the prevalence of PD will have greater impact within the Department of Veterans Affairs (VA) because the Veteran population is older than the general population and Veterans with PD are more likely than those without PD to rely solely on VA for their health care. While PD is often characterized by the motor symptoms of the disease (tremor, bradykinesia, rigidity), non-motor symptoms such as urinary symptoms correlate more closely with impaired well-being as the disease progresses. However, the impact of urinary symptoms in PD extends beyond worsened well-being. The urinary symptoms of overactive bladder (OAB), including urgency, frequency, and nocturia, with or without urinary incontinence, are the most common urinary symptoms of PD. OAB symptoms are associated with falls (a cause of increased mortality in PD), with spouse/caregiver stress, and, ultimately with institutionalization, thus it is critical that we optimize the care of urinary symptoms for Veterans with PD.

Several studies suggest abnormal central nervous system processing of sensory input from bladder afferent nerves contributes to OAB symptoms in PD, possibly because of delayed recognition of bladder fullness. This mirrors findings in non-PD populations with OAB. In the non-PD OAB population, pelvic floor muscle contractions diminish bladder muscle contraction and recent evidence demonstrates that behavioral training with pelvic floor muscle exercises improves the cortical integration of bladder afferent signals. Pelvic floor muscle exercise-based behavioral therapy for OAB symptoms requires individuals to learn a motor skill and implement an adaptive behavioral strategy to delay the need to void. Because of its effectiveness compared to drug therapy, pelvic floor muscle exercise-based behavioral therapy is recommended first-line in men and women with OAB who do not have PD. However, the most recent clinical guidelines for the treatment of urinary symptoms in PD recommend treatment with anticholinergic drugs. While some anticholinergic drugs are effective in reducing symptoms of OAB, it is important to note that there is a glaring lack of an empirical evidence base to promote these drugs in the setting of PD given that they add to the anticholinergic burden of antiparkinsonian therapy, and may worsen the cognitive and autonomic burdens of the illness. Therefore, randomized controlled trials (RCTs) are needed to optimize treatment paradigms for urinary symptoms in PD.

The investigators propose a three-site, RCT conducted at the Atlanta (lead site), Birmingham and Richmond VA's to establish non-inferiority of pelvic floor muscle exercise-based behavioral therapy compared to drug therapy for OAB symptoms in adults with PD. Groups will be stratified by OAB symptom severity, PD motor symptom severity, gender, and site. The investigators will randomize 90 participants in order to complete the study in 80 participants, assuming 85% power and a non-inferiority margin for the OAB symptom score of 15% at 12-weeks. The primary outcome measure will be urinary symptom severity as measured by the International Consultation on Incontinence Questionnaire (ICIQ)-OAB symptom score collected at 3 time points during the study: baseline, 6 weeks, and 12 weeks. The investigators' benchmark for successful treatment will be a 2 point reduction in the ICIQ-OAB symptom score, which corresponds with perceived benefit in preliminary studies of behavioral therapy treatment for OAB symptoms in PD. To evaluate the primary efficacy outcome, the investigators will utilize a random effects mixed model and adjust for baseline OAB symptom score severity. Additionally, in order to better understand central control mechanisms of bladder function, the investigators will determine if domain-specific cognitive function impacts the response to exercise-based behavioral therapy or drug therapy for urinary symptoms. At baseline and 12 weeks, randomized participants will undergo a brief neuropsychological battery. Understanding how domain-specific cognitive function impacts response to treatment may inform new targets for rehabilitation therapy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized Controlled Non-Inferiority TrialRandomized Controlled Non-Inferiority Trial

Masking:

Single (Outcomes Assessor)

Masking Description:

Blinded assessor

Primary Purpose:

Treatment

Official Title:

Behavioral or Solifenacin Therapy for Urinary Symptoms in Parkinson Disease

Actual Study Start Date :

Mar 1, 2018

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Behavioral therapy Pelvic floor muscle exercise-based behavioral therapy	Behavioral: Pelvic floor muscle exercise-based behavioral therapy Multicomponent intervention including fluid management, constipation management and behavioral techniques incorporating pelvic floor muscle-exercise based urge suppression and self-monitoring to reduce overactive bladder symptoms
Active Comparator: Drug Therapy Daily solifenacin drug therapy	Drug: solifenacin Antimuscarinic bladder relaxant, antagonizes bladder muscarinic receptors Other Names: Vesicare

Arm

Intervention/Treatment

Active Comparator: Behavioral therapy

Pelvic floor muscle exercise-based behavioral therapy

Behavioral: Pelvic floor muscle exercise-based behavioral therapy

Multicomponent intervention including fluid management, constipation management and behavioral techniques incorporating pelvic floor muscle-exercise based urge suppression and self-monitoring to reduce overactive bladder symptoms

Active Comparator: Drug Therapy

Daily solifenacin drug therapy

Drug: solifenacin

Antimuscarinic bladder relaxant, antagonizes bladder muscarinic receptors

Other Names:

Vesicare

Outcome Measures

Primary Outcome Measures

ICIQ-OAB questionnaire [change from baseline in symptom score at 12 weeks within and between groups]
The ICIQ-OAB questionnaire is a 4-question assessment of OAB symptoms and the degree to which they bother the respondent (urgency, frequency, nocturia, UI).

Secondary Outcome Measures

Bladder diary [change from baseline in weekly incontinence frequency at 12 weeks within and between groups]
7-day bladder diary includes daily participant-reported voids and incontinent episodes, with ratings of associated urgency, and wake time and bedtime to assess daytime frequency and nocturia
ICIQ-OAB QOL [change from baseline in QOL score at 12 weeks within and between groups]
Assessment of quality of life related to the impact of overactive bladder symptoms on daily activities

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Clinical diagnosis of PD determined by a board-certified neurologist with specialty training in movement disorders
An ICIQ-OAB Symptom Score of 7, which indicates clinically significant symptoms of OAB, defined as presence of urinary urgency with or without urgency incontinence usually with increased daytime frequency and nocturia in the absence of infection or other obvious pathology

Exclusion Criteria:

Significant cognitive impairment, as indicated by a Montreal Cognitive Assessment (MoCA) score of < 18, which is the recommended diagnostic cutpoint for dementia in PD.
Previous intensive pelvic floor muscle exercise training
Clinically significant depression as measured by a Geriatric Depression Scale-Short Form score 10 which could affect motivation to fully engage in the intervention
Use of an indwelling urinary catheter
Post-void residual (PVR) urine measurement by bladder ultrasound of 150 mL
Severe uterine prolapse past the vaginal introitus
Poorly controlled diabetes defined by a hemoglobin A1c (HgbA1c) of >9.0% within the last 3 months. Participants with poorly controlled diabetes will be offered enrollment if the OAB symptoms persist after improvement in diabetes control
Chronic renal failure and on hemodialysis
Genitourinary cancer with ongoing surgical or external beam radiation treatment
Previous artificial urinary sphincter, sling procedure or implanted sacral neuromodulation device
History of bladder-injection of botulinum toxin in the last 12 months
Any unstable health condition expected to result in hospitalization or death within in the next 3 months as determined by site principal investigator.
Hypersensitivity to drug class
Contraindication to the study drug (solifenacin) including: narrow angle glaucoma, history of gastric retention, history of acute urinary retention requiring catheterization
Current use of a bladder relaxant - permitted to enroll after two week washout
Hematuria on microscopic examination in the absence of infection. A urologic consultation will be recommended and enrollment will depend on clearance by a urologist and agreement by the site PI that entry into the treatment protocol is not contraindicated
If on diuretic, dose should be stable for at least 4 weeks
If taking an alpha-blocker, dose should be stable for at least 4 weeks
If taking dutasteride or finasteride, dose should be stable for at least 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham VA Medical Center, Birmingham, AL	Birmingham	Alabama	United States	35233
2	Atlanta VA Medical and Rehab Center, Decatur, GA	Decatur	Georgia	United States	30033
3	Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA	Philadelphia	Pennsylvania	United States	19104
4	Hunter Holmes McGuire VA Medical Center, Richmond, VA	Richmond	Virginia	United States	23249